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Biomedical subjects

J Charrier

Publications and source records attributed to J Charrier.

At least 19 recordsLinked to original sources
PubMed2001

Genetic polymorphism at the glutathione S-transferase (GST) P1 locus is a breast cancer risk modifier.

The isolation of full-length cDNAs of naturally occurring GSTP1 gene variants, and the demonstration that these alleles are distributed in the normal population, have provided conclusive evidence that the human GSTP1 gene locus is polymorphic and that specific GSTP1 alleles may be associated with different risk for cancers or other diseases. Recent data have indicated that the different GSTP1 alleles encode proteins with different enzymatic activities against carcinogens. In this case-control study, we examined the effect of the GSTP1 genetic polymorphism and its interaction with other factors to determine breast cancer risk. GSTP1 and GSTM1 genotypes of 220 breast cancer patients and 196 controls, all residents of western France, were examined. Data on menopausal status and family cancer history were obtained from 195 patients and 147 controls. Exons 5 and 6 of the GSTP1 gene, which contain the polymorphic nucleotide transitions, were analyzed by DNA polymerase chain reaction-restriction fragment length polymorphism to distinguish between the GSTP1 alleles. In the control population, GSTP1 allelic frequencies were 64.3%, 26.0% and 9.7%, respectively, for GSTP1*A, GSTP1*B and GSTP1*C. In the breast cancer patients, the frequencies were 67.9% for GSTP1*A, 26.8% for GSTP1*B and 5.3% for GSTP1*C. In multivariate analysis, breast cancer risk increased by 7.7-fold (p < 0.001) in women with a family history of cancers and 2.18-fold (p = 0.026) in non-GSTP1*C individuals. GSTM1 genotypes did not emerge as risk factor. Our results show that in addition to well-known risk factors, in particular, a family history of cancer, GSTP1 allelopolymorphism is a significant modifier of breast cancer risk. The results also suggest a protective role against breast cancer for the GSTP1*C allele.

Adult↗
PubMed1999

Allelotype influence at glutathione S-transferase M1 locus on breast cancer susceptibility.

The influence of polymorphisms of the glutathione S-transferase gene GSTM1 in breast cancer susceptibility has been assessed in this study. Previous studies correlated the absence of the GSTM1 protein with an increased risk of developing some cancers, especially lung or bladder cancers, in heavy smokers. In this study, we determined GSTM1 polymorphisms in a population of 437 female controls from the west of France and 361 community breast cancer patients. Three distinct alleles of this gene exist: GSTM1*A, GSTM1*B and GSTM1*0 (deleted allele). Null subjects (GSTM1 null) are homozygous for this deletion. The comparative analysis of GSTM1 allelotypes in our two populations did not demonstrate a statistically significant difference in distribution (P = 0.22), although the null genotype was more frequent in cancer patients. However, breast cancer risk was increased in null subjects > or = 50 years of age compared with non-null subjects [odds ratio = 1.99 (1.19-3.32), P = 0.009], but not in null subjects < 50 years of age compared with non-null subjects (P = 0.86). Our results suggest that the GSTM1 null genotype may play a role in post-menopausal breast cancer development. They also point to a putative protective role of the A allele in the older female control group, especially in hemizygous subjects [odds ratio = 0.42 (0.23-0.77), P = 0.03].

Adult↗
PubMed1998

Allelic deletion at glutathione S-transferase M1 locus and its association with breast cancer susceptibility.

Glutathione S-transferases (GSTs) are a family of isoenzymes involved in cellular detoxification. Previous studies have correlated the absence of the GSTM1 protein with an increased risk of developing some cancers, especially lung or bladder cancer, in heavy smokers. In this study, we determined GSTM1 gene polymorphisms in a French western population of 437 female controls and 361 community breast cancer patients. Three distinct alleles of this gene may be identified: GST M1* A allele, GST M1* B allele, and GST M1* 0 allele (which is deleted). Null patients (GSTM1 0) are homozygous for the deletion. We determined in our two populations, patients with no, one or two GSTM1 alleles. The comparative analysis of our two populations did not demonstrate any statistically significant difference in GSTM1 allelotype distribution between the two groups (P = 0.43), although the null genotype was the more frequent in patients. The predominance of the null genotype was significant in the oldest group of patients (> or = 55) (P = 0.006), suggesting that GSTM1 null genotype may play an important role in breast cancer susceptibility in the elderly. This was not observed in the youngest age group, i.e. < 40 year old patients (P = 0.25), or in the patients aged from 40 to 55 years old (P = 0.37). Our results also point out a putative protective role of the A allele in the older female control group (P = 0.02), especially in subjects hemizygous for these alleles (P = 0.03). A prospective study will be of interest to investigate the effect of dosage of the gene.

Adult↗
PubMed1997

French multicentric evaluation of mdr1 gene expression by RT-PCR in leukemia and solid tumours. Standardization of RT-PCR and preliminary comparisons between RT-PCR and immunohistochemistry in solid tumours. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique-Hôpitaux de Paris.

Since there is no consensus on the techniques for multidrug resistance (MDR) phenotype evaluation, many discrepancies concerning the importance and frequency of mdr1 gene expression in leukemias and solid tumors are observed in the literature. In order to establish an inter-laboratory consensus in France, a multicenter study was carried out to propose further guidelines for MDR phenotype evaluation. The techniques used by the 38 laboratories participating in the trial were: immunodetection (immunohisto and/or cytochemistry, flow cytometry), functional tests, reverse transcription-polymerase chain reaction (RT-PCR) or Northern blot. We present the results obtained by 19 laboratories concerning the measurement of mdr1 gene expression assessed by RT-PCR or Northern blot in: (1)19 samples of tumor cells obtained from leukemic patients; (2) six solid tumor samples obtained at surgery; (3) eight cell lines exhibiting variable levels of resistance, and; (4)10 preparations of RNA and of cDNA obtained from solid tumors. Standardization of the RT-PCR technique and preliminary results comparing RT-PCR with immunohistochemistry in solid tumors are also reported.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Chemotherapeutic inhibition of erb-B2 oncogene expression on a non-small-cell cancer line (NSCLC-N6) by marine substances.

The inhibitory effect of natural substances of marine origin on the erb-B2 oncogene of a human NSCLC-N6 line was demonstrated in vitro by simultaneous study of the expression of the gene and its product, using respectively an erb-B2 specific probe and an anti-c-erb-B2 polyclonal antibody. Preliminary results indicate inhibition ranging from 17-77% of oncogene expression and from 77-90% of product expression. The fact that substances of this type, with different chemical structures, have the common ability to induce terminal differentiation in an experimental model after irreversible blockade in G1 phase suggests a relationship between the inhibition of certain oncogenes and terminal differentiation.

Acetamides↗
PubMed1992

Effects of insulin-like growth factor-I (IGF-I) infusion and dietary tri-iodothyronine (T3) supplementation on growth, body composition and plasma hormone levels in sex-linked dwarf mutant and normal chickens.

This study used a sex-linked dwarf mutant (SLD) chicken to evaluate growth-promoting and metabolic effects of recombinant human insulin-like growth factor-I (rhIGF-I) treatment. The SLD chicken is characterized by a 30% reduction in body weight and by high plasma GH levels, low plasma IGF-I and triodothyronine (T3) levels and very low GH binding on liver membranes, suggesting reduced functional GH receptors compared with normal chickens. The effects of a continuous s.c. infusion by osmotic mini-pump of 0.1 mg rhIGF-I/kg per day from 4 to 8 weeks of age on body weight, bone growth and body composition were investigated in female SLD and normal chicks. In addition, half of the birds received a dietary supplement of T3 (0.1 parts per million). Plasma levels of IGF-I, GH, T3, thyroxine and insulin were followed during the treatment. In normal chicks, rhIGF-I infusion had no effect on growth and little effect on plasma hormone levels except for a decrease in plasma insulin. In dwarf chicks, rhIGF-I infusion slightly increased body weight but had no effect on longitudinal bone growth. In addition, plasma GH levels were decreased and T3 levels remained lower than in normal chicks. Normal and dwarf chicks showed a decrease in abdominal fat after both IGF-I administration and T3 supplementation, the treatments having additive effects in dwarf chicks only. The combined rhIGF-I and T3 treatment restored a quasi-normal hormonal pattern in dwarf chicks, except for insulin which remained lower than in normal chicks. These results suggest that IGF-I in the chicken has no direct endocrine effect on statural growth.

Animals↗
PubMed1991

GRF treatment of late pregnant ewes alters maternal and fetal somatotropic axis activity.

To examine the effects of anabolic agents given during late gestation on the maternal and fetal somatotropic axes, we injected pregnant ewes twice daily with 0.15 mg somatocrinin (GRF)-(1-29) for 10 days beginning on day 130 of gestation. Maternal and fetal endocrine changes were compared with control animals using both in vivo and in vitro approaches. Treatment with GRF increased maternal plasma levels of growth hormone (GH) and insulin-like growth factor I (IGF-I;P less than 0.05) but not IGF-II. Under in vitro test conditions, maternal pituitary cells showed a greater maximal response (P less than 0.001) to GRF. In the fetuses of treated ewes, cord plasma GH levels were not significantly increased compared with controls. These animals had similar IGF-I but higher IGF-II (P less than 0.05) plasma levels. The maximal response of fetal pituitary cells to GRF was increased (P less than 0.001). GRF treatment had no influence on maternal and fetal pituitary cell responses to somatostatin under either basal or GRF-stimulated conditions. In addition, these treatments did not affect plasma levels of placental lactogen, glucose, or free fatty acids in the maternal and fetal sheep. These data are compatible with the hypothesis that treatment of pregnant ewes in the last days of gestation with GRF could support accelerated fetal growth.

Animals↗
PubMed1990

Application of preparative high-performance liquid chromatography to the purification of a fetal ovine insulin-like growth factor II: N-terminal sequence determinations using two different carriers.

A highly efficient procedure for the purification to homogeneity of an ovine fetal insulin-like growth factor II (IGF II) is described. Fetal sheep serum was used as the source material, and the bioactivity was followed throughout purification by an IGF II radioreceptor assay. Ovine IGF II was isolated by a combination of gel permeation, ion-exchange chromatography and reversed-phase high-performance liquid chromatography. The amino-terminal sequence of the first 36 amino acid residues was compared using two supports (polyethylenimine and polybrene) as carrier for protein sequencing. Ovine fetal IGF II was found to differ from human IGF II in three residues of the C-domain, with serine, isoleucine and asparagine substituted for alanine, valine and serine, respectively, at positions 32, 35 and 36. The final yield of highly purified ovine fetal IGF II was 134 micrograms, starting from 450 ml of serum.

Amino Acid Sequence↗
PubMed1989

Effects of a chronic GRF treatment on lambs having low or normal birth weight.

The effects of a long term treatment with human GRF(1-29)NH2 on plasma growth hormone (GH), somatomedin C (Sm-C), histomorphometric parameters of bone growth and body composition were investigated in normal and low birthweight male lambs. The animals were divided into two groups according to their birthweight: 24 normal birthweight (NBW) lambs weighing more than 4 kg and 22 low birthweight (LBW) lambs weighing less than 2.5 kg at birth. Half of the animals in each group received two daily subcutaneous injections (8 micrograms/kg body weight) of hGRF(1-29) NH2 (GRF) from birth to slaughter at 45 or 90 days of age. The other animals received the solvent only. At the beginning and at the end of the treatment, plasma GH and serum Sm-C concentrations were measured in all groups. After slaughter, a histomorphometric study was performed on undecalcified sections of metacarpal growth plates, and the remaining of the carcass was pulverized to study the chemical body composition. GRF induced GH release in both GRF-treated groups. However, plasma GH reached higher (P less than .001) concentrations and the GRF-induced GH peak lasted longer in LBW than in NBW lambs. At day 45, the GRF treatment increased (P less than .05) serum Sm-C concentrations in LBW. Most of histomorphometric parameters reflecting the metacarpal growth in length, were not statistically modified under GRF treatment. However, the size of degenerative cells was smaller (P less than .05) in LBW treated lambs as compared to controls. Consequently, the cell production in the growth plate was increased (P less than .05) under GRF treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Growth hormones. II. Structure-function relationships.

Localization of the somatotropic activity of growth hormones from several species and from different organs was attempted using different approaches. Sequences were compared in order to detect one or several regions with a common homology. The technique of peptide recombinants as well as chemical changes affecting some amino acids was applied to these hormones; the biological function in vivo of growth or binding to somatotropic receptors was then estimated. The few data available on biosynthetic molecules and secondary structures of natural growth hormones are reported. This study indicates the somatotropic function of particular sites.

Amino Acid Sequence↗
PubMed1989

Instantaneous secretion rate of growth hormone in lambs: relationships with sleep, food intake, and posture.

Relationships among sleep, feeding behavior, posture, and GH secretion were investigated in two groups of ruminant lambs in January (n = 6) and May (n = 3). Lambs were placed in individual cages and fed ad libitum. Behavioral features were obtained from continuous polygraphic recording. Blood was collected from undisturbed sheep every 3 min for 24 h via an indwelling catheter connected to a peristaltic pump. One month after the sampling session, ovine GH (oGH) was iv administered to evaluate oGH kinetic parameters. From GH plasma concentrations and oGH kinetic parameters, the instantaneous secretion rate of GH was reconstituted using a numerical deconvolution method. All lambs exhibited normal behavioral patterns. The clearance of oGH was similar for the two groups, and the daily production rates of GH were estimated at 14.60 +/- 7.99 micrograms/kg.24 h in January and 10.57 +/- 5.21 micrograms/kg.24 h in May. Analysis of concentration profiles indicate an episodic pattern of GH secretion into plasma. The mean number of peaks was 16.22 +/- 4.47/24 h, and the mean duration was 47.2 +/- 12.8 min for the nine sheep. When instantaneous secretion rates were taken into account, the number of identified peaks was similar, but the mean duration was reduced (32.9 +/- 9.8 min for the nine sheep). Significant relationships were not found between GH plasma concentration profiles and the state of vigilance, food behavior, or posture. Conversely, when the instantaneous secretion rates were taken into account, the highest GH production rate was detected during rest, i.e. slow wave sleep and rapid eye movement sleep, absence of food intake or rumination, and lying down. It is emphasized that the use of GH instantaneous secretion rate instead of GH concentration is of importance when evaluating the relationships between GH dynamics and short duration events. It is concluded that the influence of vigilance on GH secretion, which has already been demonstrated in humans, is likely to exist in other species.

Animals↗
PubMed1988

Growth hormones. 1. Polymorphism (minireview).

Pituitary growth hormone (GH) is not a single molecular species, but a whole set of similar molecules, the individual specific characteristics of which constitute the polymorphism of this hormone. The present paper deals mainly with various forms of human GH, called "variants", and touches on this polymorphism in other species as well. The 22 K variant (MW = 22,000 daltons) is the predominant form of GH to which all other variants are compared as to chemical structure and biological effect. These variants are classified into two large groups: 1) mass variants, the molecular weight of which is modified in comparison with that of 22 K; these can be subdivided into aggregated and non-aggregated forms, and 2) charge variants with modified electrophoretic mobility. Outside this classification are entities which are not yet well known; these include bioinactive GH, correctly detected by RIA but deprived of biological activity or, on the contrary, strongly bioactive GH lacking immunoreactivity and consequently difficult to study. Another outsider is the SV-hGH-2 variant encoded from a gene different from the hGH-N gene normally coding for the other variants. In this case, the product could be considered a true isohormone of 22 K and no longer a variant. The pituitary expression of this gene has never been evidenced to date, but according to recent data, it could be expressed at the placental level and be implicated in human placental growth hormone (hPGH) synthesis. hPGH is a newly-found GH in pregnant women which takes over pituitary GH from the 25th week onwards. After the GH molecules are released by the pituitary in the blood stream, they are partially taken up and carried by binding proteins. The physiological role of this phenomenon could be the setting up of a GH reservoir and a GH sparing process since the metabolic clearance rate of the complex GH-binding protein is slower than that of free GH, thus increasing the biological half-life of the hormone.

Animals↗
PubMed1988

Ovine chorionic somatomammotropin and foetal growth.

Ovine chorionic somatomammotropin (oCS) enhances the weight and bone growth of hypophysectomized rats. It acts as a bifunctional hormone, since it binds both to lactogenic and somatotropic receptors. Ovine foetus weight gain is closely related to oCS and oGH serum levels. oCS is able to stimulate somatomedins by foetal liver. Moreover, oCS specific receptors are present in some foetal tissues. So, all these facts involve oCS in foetal growth, whereas pituitary growth hormone intervenes in postnatal growth. A study of structure function relationships between growth hormones and placental hormones is exposed in order to localize somatotropic sites.

Animals↗
PubMed1988

In vitro regulation of growth hormone (GH) release from ovine pituitary cells during fetal and neonatal development: effects of GH-releasing factor, somatostatin, and insulin-like growth factor I.

Using a monolayer approach, we have examined the acute (3 h) effects of GRF, somatostatin (SRIF), and insulin-like growth factor I (IGF-I) on GH release from pituitary cells of male and female 70-, 100-, and 130-day-old fetuses and newborn lambs and of prepubertal male lambs. GRF stimulated basal GH release in a dose-dependent (10(-12)-10(-8) M) manner at each stage in development. There was no linear relationship between maximal response and increasing age of the donor animals. The ED50 values for GRF were similar in all groups, except in the pituitaries from male and female 130-day-old fetuses, where the ED50 values were significantly higher. SRIF elicited a dose-related (10(-10)-10(-6) M) inhibition of basal GH secretion at each stage of fetal life and in the prepubertal period; although the response was lower in the youngest fetal pituitaries, there was no significant change in maximal response during the fetal or prepubertal period. No effect of SRIF on basal GH secretion was observed in newborn lambs. However, SRIF (10(-7) M) was able to block GRF (10(-8) M)-stimulated GH release in 100- and 130-day-old fetal and prepubertal as well as newborn lamb pituitary cells. Plasma IGF-I concentrations increased from 15.0 +/- 0.7 (mean +/- SE) and 13.8 +/- 0.9 ng/ml for male and female animals, respectively, at 70 days gestation to 55.8 +/- 3.2 and 51.8 +/- 11.1 ng/ml at the time of birth. The increase was much more pronounced in prepubertal lambs, especially in male animals, where IGF-I levels reached 300.8 +/- 37.7 ng/ml. IGF-I (100 ng/ml) had no effect on basal GH release in 70- and 100-day-old fetal, newborn, and prepubertal lamb pituitary cultures, but significantly inhibited basal GH secretion from 130-day-old fetal cells. This dose of IGF-I had no effect on GRF (10(-9) M)-stimulated GH release at 70 days gestation. It significantly inhibited this effect at 100 days and in prepubertal lamb cells. In 130-day-old fetal and newborn lamb pituitary cultures, IGF-I completely blocked the GH response to GRF.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1988

[Effects of GRF 1-29 in normal and hypotrophic lambs].

Injections of hGRF rapidly stimulated GH secretion in lamb and this response was significantly higher in hypotrophic than in normal lambs. The treatment had an effect on body composition reducing the retention of lipids and the energy level and increasing calcium and phosphorus content. The results showed that GRF affected both metabolism and skeletal growth of ruminants, stimulating specially the production of Sm-C and proliferation of chondrocytes.

Animals↗